SK9032000A3 - Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists - Google Patents

Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists Download PDF

Info

Publication number: SK9032000A3
Authority: SK; Slovakia
Prior art keywords: alkyl; group; carbon atoms; aryl; formula
Prior art date: 1997-12-19

Application number

SK903-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Anuschirvan Peyman

Gerhard Breipohl

Denis Carniato

Jochen Knolle

Karl-Heinz Scheunemann

Jean-Francois Gourvest

Thomas R Gadek

Robert Mcdowell

Sarah Catherine Bodary

Robert Andrew Cuthbertson

Napoleane Ferrara

Original Assignee

Aventis Pharma Gmbh

Genentech Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-12-19

Filing date

1998-12-10

Publication date

2001-04-09

1998-12-10 Application filed by Aventis Pharma Gmbh, Genentech Inc filed Critical Aventis Pharma Gmbh

2001-04-09 Publication of SK9032000A3 publication Critical patent/SK9032000A3/sk

Links

208000006386 Bone Resorption Diseases 0.000 title claims abstract description 19
102100022337 Integrin alpha-V Human genes 0.000 title claims abstract description 19
108010048673 Vitronectin Receptors Proteins 0.000 title claims abstract description 19
230000024279 bone resorption Effects 0.000 title claims abstract description 19
239000003112 inhibitor Substances 0.000 title claims abstract description 11
239000002464 receptor antagonist Substances 0.000 title claims abstract description 9
229940044551 receptor antagonist Drugs 0.000 title claims abstract description 9
150000001875 compounds Chemical class 0.000 claims abstract description 120
150000003839 salts Chemical class 0.000 claims abstract description 64
229940002612 prodrug Drugs 0.000 claims abstract description 57
239000000651 prodrug Substances 0.000 claims abstract description 57
238000000034 method Methods 0.000 claims abstract description 21
238000011321 prophylaxis Methods 0.000 claims abstract description 21
208000001132 Osteoporosis Diseases 0.000 claims abstract description 12
230000008569 process Effects 0.000 claims abstract description 11
238000002360 preparation method Methods 0.000 claims abstract description 9
238000002560 therapeutic procedure Methods 0.000 claims abstract description 9
125000004432 carbon atom Chemical group C* 0.000 claims description 90
125000000217 alkyl group Chemical group 0.000 claims description 54
-1 4- (2 (1,4,5,6-tetrahydropyrimidin-2-ylcarbamoyl) ethyl) benzoylamino Chemical group 0.000 claims description 48
125000003118 aryl group Chemical group 0.000 claims description 44
239000000203 mixture Substances 0.000 claims description 38
229920006395 saturated elastomer Polymers 0.000 claims description 35
239000001257 hydrogen Substances 0.000 claims description 33
229910052739 hydrogen Inorganic materials 0.000 claims description 33
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
125000002947 alkylene group Chemical group 0.000 claims description 21
125000000753 cycloalkyl group Chemical group 0.000 claims description 19
125000005842 heteroatom Chemical group 0.000 claims description 19
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 19
125000001072 heteroaryl group Chemical group 0.000 claims description 18
239000002253 acid Substances 0.000 claims description 17
125000002837 carbocyclic group Chemical group 0.000 claims description 17
125000000623 heterocyclic group Chemical group 0.000 claims description 17
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 15
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
229910052736 halogen Inorganic materials 0.000 claims description 15
150000002367 halogens Chemical class 0.000 claims description 15
239000008194 pharmaceutical composition Substances 0.000 claims description 15
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 14
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 12
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 12
206010028980 Neoplasm Diseases 0.000 claims description 11
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
125000000524 functional group Chemical group 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
239000001301 oxygen Substances 0.000 claims description 9
150000002357 guanidines Chemical class 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
125000004430 oxygen atom Chemical group O* 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 6
150000001450 anions Chemical class 0.000 claims description 6
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 6
239000003814 drug Substances 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
239000002243 precursor Substances 0.000 claims description 5
206010003210 Arteriosclerosis Diseases 0.000 claims description 4
208000024172 Cardiovascular disease Diseases 0.000 claims description 4
206010027476 Metastases Diseases 0.000 claims description 4
208000017442 Retinal disease Diseases 0.000 claims description 4
206010038923 Retinopathy Diseases 0.000 claims description 4
208000011775 arteriosclerosis disease Diseases 0.000 claims description 4
230000009401 metastasis Effects 0.000 claims description 4
125000004043 oxo group Chemical group O=* 0.000 claims description 4
208000037803 restenosis Diseases 0.000 claims description 4
230000004614 tumor growth Effects 0.000 claims description 4
GWIKTGZMCPFFRW-NRFANRHFSA-N (2s)-3-[4-[4-oxo-4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)butoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1OCCCC(=O)NC1=NCCCN1 GWIKTGZMCPFFRW-NRFANRHFSA-N 0.000 claims description 3
QUEYKBRMKHRYJV-IBGZPJMESA-N (2s)-3-[[4-[2-oxo-2-(1,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl]amino]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)NC(=O)C(C=C1)=CC=C1OCC(=O)NC1=NCCCN1 QUEYKBRMKHRYJV-IBGZPJMESA-N 0.000 claims description 3
229940121363 anti-inflammatory agent Drugs 0.000 claims description 3
239000002260 anti-inflammatory agent Substances 0.000 claims description 3
208000017169 kidney disease Diseases 0.000 claims description 3
231100000252 nontoxic Toxicity 0.000 claims description 3
230000003000 nontoxic effect Effects 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 2
239000012634 fragment Substances 0.000 claims description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 4
235000019260 propionic acid Nutrition 0.000 claims 2
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
210000002997 osteoclast Anatomy 0.000 abstract description 18
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239000004480 active ingredient Substances 0.000 abstract description 9
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DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 30
210000004027 cell Anatomy 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 17
238000011282 treatment Methods 0.000 description 17
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
239000000872 buffer Substances 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
238000004949 mass spectrometry Methods 0.000 description 12
239000002904 solvent Substances 0.000 description 12
125000001424 substituent group Chemical group 0.000 description 11
239000000047 product Substances 0.000 description 10
210000000988 bone and bone Anatomy 0.000 description 9
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000000741 silica gel Substances 0.000 description 7
229910002027 silica gel Inorganic materials 0.000 description 7
238000003756 stirring Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000005557 antagonist Substances 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000000969 carrier Substances 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
229940011871 estrogen Drugs 0.000 description 6
239000000262 estrogen Substances 0.000 description 6
150000002431 hydrogen Chemical class 0.000 description 6
230000003993 interaction Effects 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
239000011593 sulfur Chemical group 0.000 description 6
239000003826 tablet Substances 0.000 description 6
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000002252 acyl group Chemical group 0.000 description 5
239000002585 base Substances 0.000 description 5
210000002805 bone matrix Anatomy 0.000 description 5
201000011510 cancer Diseases 0.000 description 5
150000001735 carboxylic acids Chemical class 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 4
208000020084 Bone disease Diseases 0.000 description 4
229940078581 Bone resorption inhibitor Drugs 0.000 description 4
125000005915 C6-C14 aryl group Chemical group 0.000 description 4
101000803709 Homo sapiens Vitronectin Proteins 0.000 description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
FPQVGDGSRVMNMR-JCTPKUEWSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-(dimethylamino)methylidene]-dimethylazanium;tetrafluoroborate Chemical compound F[B-](F)(F)F.CCOC(=O)C(\C#N)=N/OC(N(C)C)=[N+](C)C FPQVGDGSRVMNMR-JCTPKUEWSA-N 0.000 description 4
230000033115 angiogenesis Effects 0.000 description 4
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
125000004185 ester group Chemical group 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
230000011164 ossification Effects 0.000 description 4
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000012360 testing method Methods 0.000 description 4
125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
108010031318 Vitronectin Proteins 0.000 description 3
102100035140 Vitronectin Human genes 0.000 description 3
238000010521 absorption reaction Methods 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
239000013543 active substance Substances 0.000 description 3
125000000129 anionic group Chemical group 0.000 description 3
108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
150000001721 carbon Chemical group 0.000 description 3
125000002843 carboxylic acid group Chemical group 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000002648 combination therapy Methods 0.000 description 3
230000006378 damage Effects 0.000 description 3
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
238000004821 distillation Methods 0.000 description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000008103 glucose Substances 0.000 description 3
235000001727 glucose Nutrition 0.000 description 3
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
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230000002401 inhibitory effect Effects 0.000 description 3
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210000001519 tissue Anatomy 0.000 description 3
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MHCYIOJZTKJCCC-FQEVSTJZSA-N (2s)-3-[4-[4-(4,5-dihydro-1h-imidazol-2-ylamino)-4-oxobutoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C(C=C1)=CC=C1OCCCC(=O)NC1=NCCN1 MHCYIOJZTKJCCC-FQEVSTJZSA-N 0.000 description 2
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PECYZEOJVXMISF-UHFFFAOYSA-N 3-aminoalanine Chemical class [NH3+]CC(N)C([O-])=O PECYZEOJVXMISF-UHFFFAOYSA-N 0.000 description 2
SPBVJVFCFLINPJ-UHFFFAOYSA-N 4-(2-methoxy-2-oxoethoxy)benzoic acid Chemical compound COC(=O)COC1=CC=C(C(O)=O)C=C1 SPBVJVFCFLINPJ-UHFFFAOYSA-N 0.000 description 2
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WDYXTBQUPCLKQQ-UHFFFAOYSA-N 4-(3-methoxy-3-oxopropyl)benzoic acid Chemical compound COC(=O)CCC1=CC=C(C(O)=O)C=C1 WDYXTBQUPCLKQQ-UHFFFAOYSA-N 0.000 description 2
ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
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229940088594 vitamin Drugs 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
235000019166 vitamin D Nutrition 0.000 description 1
239000011710 vitamin D Chemical class 0.000 description 1
150000003710 vitamin D derivatives Chemical class 0.000 description 1
229940046008 vitamin d Drugs 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4168—1,3-Diazoles having a nitrogen attached in position 2, e.g. clonidine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/48—Nitrogen atoms not forming part of a nitro radical with acyclic hydrocarbon or substituted acyclic hydrocarbon radicals, attached to said nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/12—Nitrogen atoms not forming part of a nitro radical
- C07D239/16—Nitrogen atoms not forming part of a nitro radical acylated on said nitrogen atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Physical Education & Sports Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Orthopedic Medicine & Surgery (AREA)
Pain & Pain Management (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Indole Compounds (AREA)

SK903-2000A 1997-12-19 1998-12-10 Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists SK9032000A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97122520A EP0933367A1 (fr)	1997-12-19	1997-12-19	Dérivés d'acylguanidine comme inhibiteurs de résorbtion osseuse et comme antagonistes de récepteur vitronectine
PCT/EP1998/008051 WO1999032457A1 (fr)	1997-12-19	1998-12-10	Nouveaux derives d'acylguanidine en tant qu'inhibiteurs de la resorption osseuse et qu'antagonistes du recepteur de vitronectine

Publications (1)

Publication Number	Publication Date
SK9032000A3 true SK9032000A3 (en)	2001-04-09

Family

ID=8227841

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK903-2000A SK9032000A3 (en)	1997-12-19	1998-12-10	Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists

Country Status (34)

Country	Link
US (1)	US6492356B1 (fr)
EP (2)	EP0933367A1 (fr)
JP (1)	JP2001526271A (fr)
KR (1)	KR20010033281A (fr)
CN (1)	CN1205191C (fr)
AP (1)	AP2000001842A0 (fr)
AR (1)	AR016437A1 (fr)
AT (1)	ATE228112T1 (fr)
AU (1)	AU753109B2 (fr)
BG (1)	BG64754B1 (fr)
BR (1)	BR9814308A (fr)
CA (1)	CA2312712A1 (fr)
CU (1)	CU23032A3 (fr)
DE (1)	DE69809594T2 (fr)
DK (1)	DK1042301T3 (fr)
EA (1)	EA002921B1 (fr)
ES (1)	ES2186251T3 (fr)
HK (1)	HK1034974A1 (fr)
HR (1)	HRP20000412A2 (fr)
HU (1)	HUP0104912A3 (fr)
ID (1)	ID26248A (fr)
IL (1)	IL136858A0 (fr)
MY (1)	MY122269A (fr)
NO (1)	NO317420B1 (fr)
NZ (1)	NZ504954A (fr)
PL (1)	PL341216A1 (fr)
PT (1)	PT1042301E (fr)
SI (1)	SI1042301T1 (fr)
SK (1)	SK9032000A3 (fr)
TR (1)	TR200001964T2 (fr)
TW (1)	TW446705B (fr)
WO (1)	WO1999032457A1 (fr)
YU (1)	YU39000A (fr)
ZA (1)	ZA9811571B (fr)

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GB9814414D0 (en)	1998-07-03	1998-09-02	Celltech Therapeutics Ltd	Chemical compounds
EP1100506A4 (fr) *	1998-07-29	2002-06-26	Merck & Co Inc	Antagonistes des recepteurs de l'integrine
GB9821061D0 (en)	1998-09-28	1998-11-18	Celltech Therapeutics Ltd	Chemical compounds
GB9826174D0 (en)	1998-11-30	1999-01-20	Celltech Therapeutics Ltd	Chemical compounds
EP1028114A1 (fr)	1999-02-13	2000-08-16	Aventis Pharma Deutschland GmbH	Nouveaux dérivés de guanidine et leur utilisation comme inhibiteurs de l'adhésion des cellules
US6518283B1 (en)	1999-05-28	2003-02-11	Celltech R&D Limited	Squaric acid derivatives
EP1065207A1 (fr)	1999-07-02	2001-01-03	Aventis Pharma Deutschland GmbH	Dérivées de la naphthyridine, procédés pour leur preparation, leur utilisation, et compositions pharmaceutique les contenant
EP1070707A1 (fr) *	1999-07-21	2001-01-24	Aventis Pharma Deutschland GmbH	Dérivés de la 1,4,5,6-tetrahydropyrimidine comme inhibiteurs de la vitronectine
US6534513B1 (en)	1999-09-29	2003-03-18	Celltech R&D Limited	Phenylalkanoic acid derivatives
US6849639B2 (en)	1999-12-14	2005-02-01	Amgen Inc.	Integrin inhibitors and their methods of use
US6455539B2 (en)	1999-12-23	2002-09-24	Celltech R&D Limited	Squaric acid derivates
EP1332132B1 (fr)	2000-04-17	2007-10-10	UCB Pharma, S.A.	Derives d'enamine comme molecules d'adhesion cellulaire
FR2808798A1 (fr) *	2000-05-09	2001-11-16	Hoechst Marion Roussel Inc	Nouveaux derives antagonistes du recepteur de la vitronectine
US6545013B2 (en)	2000-05-30	2003-04-08	Celltech R&D Limited	2,7-naphthyridine derivatives
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JP2004502762A (ja)	2000-07-07	2004-01-29	セルテック　アール　アンド　ディ　リミテッド	二環性ヘテロ芳香環を含有するインテグリンアンタゴニストとしてのスクエア酸誘導体
EP1176145A1 (fr) *	2000-07-28	2002-01-30	Aventis Pharma Deutschland GmbH	Nouveaux dérivés de guanidine et leur utilisation comme inhibiteurs de l'adhésion des cellules
AU2001275724A1 (en)	2000-08-02	2002-02-13	Celltech R&D Limited	3-substituted isoquinolin-1-yl derivatives
EP1197488A1 (fr) *	2000-10-10	2002-04-17	Aventis Pharma Deutschland GmbH	Ester isopropylique de l' acide (2s)-2-(adamantyl1-méthoxycarbonylamino)-3-(4-(2-(1,4,5,6-tétrahydropyrimidin-2-ylcarbamoyl)éthyl)benzoylamino)propionique, sa préparation et son usage
FR2847254B1 (fr) *	2002-11-19	2005-01-28	Aventis Pharma Sa	Nouveaux derives antagonistes du recepteur de la vitronectine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les refermant
FR2870541B1 (fr)	2004-05-18	2006-07-14	Proskelia Sas	Derives de pyrimidines antigonistes du recepteur de la vitronectine
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
FR2873585B1 (fr) *	2004-07-27	2006-11-17	Aventis Pharma Sa	Nouvelles formulations galeniques de principes actifs
US20060039949A1 (en) *	2004-08-20	2006-02-23	Nycz Jeffrey H	Acetabular cup with controlled release of an osteoinductive formulation
US20060057184A1 (en) *	2004-09-16	2006-03-16	Nycz Jeffrey H	Process to treat avascular necrosis (AVN) with osteoinductive materials
US8414907B2 (en)	2005-04-28	2013-04-09	Warsaw Orthopedic, Inc.	Coatings on medical implants to guide soft tissue healing
US9119901B2 (en) *	2005-04-28	2015-09-01	Warsaw Orthopedic, Inc.	Surface treatments for promoting selective tissue attachment to medical impants
US20070077267A1 (en) *	2005-10-03	2007-04-05	Sdgi Holdings, Inc.	Bioactive composite implants
US20070280986A1 (en) *	2006-06-01	2007-12-06	Carlos Gil	Intra-operative coating of implants
US8133553B2 (en)	2007-06-18	2012-03-13	Zimmer, Inc.	Process for forming a ceramic layer
US8309521B2 (en)	2007-06-19	2012-11-13	Zimmer, Inc.	Spacer with a coating thereon for use with an implant device
US8608049B2 (en)	2007-10-10	2013-12-17	Zimmer, Inc.	Method for bonding a tantalum structure to a cobalt-alloy substrate
WO2009096945A1 (fr) *	2008-01-29	2009-08-06	Zimmer, Inc.	Dispositif d'implant destiné à être utilisé dans un système d'implant
KR20160147007A (ko)	2014-05-30	2016-12-21	화이자 인코포레이티드	선택적인 안드로겐 수용체 조절제로서의 카보니트릴 유도체
US11020160B2 (en)	2016-03-21	2021-06-01	Warsaw Orthopedic, Inc.	Surgical injection system and method
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1997
- 1997-12-19 EP EP97122520A patent/EP0933367A1/fr not_active Withdrawn
1998
- 1998-08-27 TW TW087110508A patent/TW446705B/zh not_active IP Right Cessation
- 1998-12-10 KR KR1020007006722A patent/KR20010033281A/ko not_active Ceased
- 1998-12-10 CU CU20000149A patent/CU23032A3/es unknown
- 1998-12-10 WO PCT/EP1998/008051 patent/WO1999032457A1/fr not_active Application Discontinuation
- 1998-12-10 CA CA002312712A patent/CA2312712A1/fr not_active Abandoned
- 1998-12-10 BR BR9814308-5A patent/BR9814308A/pt not_active Application Discontinuation
- 1998-12-10 DK DK98966287T patent/DK1042301T3/da active
- 1998-12-10 NZ NZ504954A patent/NZ504954A/en unknown
- 1998-12-10 AU AU22700/99A patent/AU753109B2/en not_active Ceased
- 1998-12-10 EP EP98966287A patent/EP1042301B1/fr not_active Expired - Lifetime
- 1998-12-10 EA EA200000682A patent/EA002921B1/ru not_active IP Right Cessation
- 1998-12-10 TR TR2000/01964T patent/TR200001964T2/xx unknown
- 1998-12-10 ID IDW20001175A patent/ID26248A/id unknown
- 1998-12-10 IL IL13685898A patent/IL136858A0/xx not_active IP Right Cessation
- 1998-12-10 AP APAP/P/2000/001842A patent/AP2000001842A0/en unknown
- 1998-12-10 PT PT98966287T patent/PT1042301E/pt unknown
- 1998-12-10 YU YU39000A patent/YU39000A/sh unknown
- 1998-12-10 PL PL98341216A patent/PL341216A1/xx not_active Application Discontinuation
- 1998-12-10 JP JP2000525394A patent/JP2001526271A/ja not_active Abandoned
- 1998-12-10 US US09/581,915 patent/US6492356B1/en not_active Expired - Fee Related
- 1998-12-10 HU HU0104912A patent/HUP0104912A3/hu unknown
- 1998-12-10 SI SI9830345T patent/SI1042301T1/xx unknown
- 1998-12-10 AT AT98966287T patent/ATE228112T1/de not_active IP Right Cessation
- 1998-12-10 CN CNB988136112A patent/CN1205191C/zh not_active Expired - Fee Related
- 1998-12-10 ES ES98966287T patent/ES2186251T3/es not_active Expired - Lifetime
- 1998-12-10 DE DE69809594T patent/DE69809594T2/de not_active Expired - Fee Related
- 1998-12-10 SK SK903-2000A patent/SK9032000A3/sk unknown
- 1998-12-17 ZA ZA9811571A patent/ZA9811571B/xx unknown
- 1998-12-17 AR ARP980106446A patent/AR016437A1/es unknown
- 1998-12-18 MY MYPI98005741A patent/MY122269A/en unknown
2000
- 2000-06-16 NO NO20003118A patent/NO317420B1/no unknown
- 2000-06-19 BG BG104544A patent/BG64754B1/bg unknown
- 2000-06-19 HR HR20000412A patent/HRP20000412A2/hr not_active Application Discontinuation
2001
- 2001-08-16 HK HK01105767A patent/HK1034974A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
BR9814308A (pt)	2000-10-10
CU23032A3 (es)	2005-03-22
HK1034974A1 (en)	2001-11-09
NO20003118D0 (no)	2000-06-16
AU753109B2 (en)	2002-10-10
HUP0104912A1 (hu)	2002-07-29
EP1042301A1 (fr)	2000-10-11
JP2001526271A (ja)	2001-12-18
ZA9811571B (en)	1999-06-21
SI1042301T1 (en)	2003-04-30
WO1999032457A1 (fr)	1999-07-01
PT1042301E (pt)	2003-04-30
US6492356B1 (en)	2002-12-10
CN1205191C (zh)	2005-06-08
DE69809594T2 (de)	2003-04-24
KR20010033281A (ko)	2001-04-25
YU39000A (sh)	2002-11-15
EP1042301B1 (fr)	2002-11-20
NO20003118L (no)	2000-08-21
DE69809594D1 (de)	2003-01-02
TW446705B (en)	2001-07-21
HUP0104912A3 (en)	2002-09-30
MY122269A (en)	2006-03-31
EA002921B1 (ru)	2002-10-31
ID26248A (id)	2000-12-07
AP2000001842A0 (en)	2000-06-30
IL136858A0 (en)	2001-06-14
HRP20000412A2 (en)	2000-10-31
ATE228112T1 (de)	2002-12-15
DK1042301T3 (da)	2003-03-17
NO317420B1 (no)	2004-10-25
AU2270099A (en)	1999-07-12
ES2186251T3 (es)	2003-05-01
EP0933367A1 (fr)	1999-08-04
PL341216A1 (en)	2001-03-26
AR016437A1 (es)	2001-07-04
NZ504954A (en)	2002-05-31
TR200001964T2 (tr)	2000-11-21
CA2312712A1 (fr)	1999-07-01
EA200000682A1 (ru)	2000-12-25
BG104544A (en)	2001-03-30
CN1284950A (zh)	2001-02-21
BG64754B1 (bg)	2006-02-28

Publication	Publication Date	Title
SK9032000A3 (en)	2001-04-09	Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists
US6566366B1 (en)	2003-05-20	Thienyl substituted acylguanidines as inhibitors of bone resorption and vitronectin receptor antagonists
NO311083B1 (no)	2001-10-08	Nye cykloalkylderivater, fremgangsmåte for fremstilling derav, farmasöytiske preparater inneholdende forbindelsene samtanvendelse av forbindelsene
JP2002501054A (ja)	2002-01-15	骨吸収の阻害剤として及び細胞接着の阻害剤としての新規のスルホンアミド誘導体
US6340679B1 (en)	2002-01-22	Guanidine derivatives as inhibitors of cell adhesion
EP1196416B1 (fr)	2004-03-24	Derives de purine a substitution en tant qu'inhibiteurs de l'adhesion cellulaire
US6602878B1 (en)	2003-08-05	Acylquanidine derivatives, method for preparing same, application as medicines and pharmaceutical compositions containing them
EP1240161B1 (fr)	2007-04-18	Derives de thienylalanine inhibiteurs d'adhesion cellulaire
US6838453B2 (en)	2005-01-04	Antagonist derivatives of the vitronectin receptor
CZ20002246A3 (cs)	2001-01-17	Derivát acylguanidinu jako inhibitor resorpce kostí jako antagonist vitronektinového receptoru
US6391904B1 (en)	2002-05-21	Iminoguanidine derivatives, preparation method, use as medicines
CZ20002672A3 (cs)	2000-12-13	Sulfonamidové deriváty jako inhibitory kostní resorpce a jako inhibitory buněčné adheze
MXPA00006068A (en)	2002-06-05	Novel acylguanidine derivatives as inhibitors of bone resorption and as vitronectin receptor antagonists